A critical goal in prostate cancer (PC) research is to identify epidemiological, clinical and molecular markers related to PC progression. We propose to conduct a follow-up study of 1200 PC patients of all ethnicities seen at U.T.M.D. Anderson Cancer Center between 1990 and 2000. These men are participants in our ongoing epidemiological studies for whom we have collected baseline clinical and epidemiological information and for whom banked specimens (DNA and tissue) are available. The objective is to identify clinical, lifestyle, and genetic factors that may play a role in disease progression. Our first aim is to evaluate baseline epidemiologic (smoking, BMI, family history of PC), clinical (stage, Gleason score, tumor volume) and treatment parameters and their impact on PC progression. We will collect information on health status through telephone interviews. Recurrence, biochemical failure, and death will be verified through medical records and death certificates. Aim 2 will evaluate genetic susceptibility by genotyping patients for polymorphic genes related to hormone metabolism: androgen receptor, 5-alpha-reductase type II, CYPO17, CYP3A4, 3-beta-hydroxysteroid dehydrogenase type II, and vitamin D receptor. In aim 3, we will create tissue microarrays to allow the analysis of gene expression by in situ hybridization for a panel for tumor progression markers (e.g., MMP-2, MMP-9, VEGF, and E-cadherin) in a subset of 375 cases of indifferent ethnicity (200 whites, 100 African Americans, and 75 Hispanics). Finally, we will integrate these molecular, epidemiologic and clinical data to investigate how the interplay between these characteristics modifies PC progression. Findings from this project could be useful in identifying patients at high risk of PC progression and could assist clinicians in determining the most appropriate strategy.